THE LATEST PCOS guidelines
At the European Society of Human Reproduction and Embryology in Copenhagen 2023 Dr Sylvia Ross attended the talks unveiling the updated guidelines for polycystic ovarian syndrome (PCOS).
At the European Society of Human Reproduction and Embryology in Copenhagen 2023 I attended the talks unveiling the updated guidelines for polycystic ovarian syndrome (PCOS). PCOS affects around 10-20% of women however it’s expected that this is a gross underestimate and up to 70% of women may remain undiagnosed. PCOS is characterized by anovulation, high androgen levels and insulin resistance. It is a leading cause of anovulation related infertility but also has very important long term health consequences including an increased risk of diabetes and heart disease. Importantly this guideline encompasses all women and recommendations are not only for those with increased body mass index as can often be assumed when considering risk profile and ongoing monitoring for development of complications.
Delay in diagnosis is common and this has shown increased morbidity for women as well as an increase in maternal age.
Diagnosis can be made entirely clinically or with the aid of bloods tests and an ultrasound scan.
Women post puberty must have two out of three of the diagnostic criteria to be diagnosed:
Irregular cycles, or no menstrual cycles (now more tightly defined at <21 or >35 days for those three years post their first period or fewer than 8 cycles per year). Absence of periods by the age of 15 or more than 3 years post breast development also prompts assessment.
Clinical or biochemical hyperandrogenism
Polycystic appearing ovaries on ultrasound scan or high AMH levels AND exclusion of other diagnoses
The update now includes the antimullarian hormone (AMH) blood test level. This is a measure of ovarian reserve which is typically high in women with PCOS indicating a large ovary and good egg stores. These women would typically expect a higher number of eggs in an IVF or egg freeze cycle. Interestingly they did not offer a cut off for this level given high variance internationally among labs however at the talks discussed they the use of 30pmol/L being a likely sensible level.
Seventy percent of women with PCOS have irregular menstrual cycles and evidence of high androgen hormone levels on their blood tests. Some will have symptoms of these high androgens which may be acne or increased hair growth. If no symptoms of high androgen levels are present then free and total testosterone should be measured and calculated. If these are not measured but suspicion remains high testing DHEAS and androstenodione can be done but these are less specific and change more with age naturally so can be harder to interpret. In women on the oral contraceptive pill these tests will not be accurate and a time period of 3 months off this medication should be instituted prior to testing if needing these results. Once these tests have been done there is no role for monitoring them long term. If the levels are well above normal range then other diagnoses must be considered.
Rarely menstruation can occur without ovulation so testing progesterone around a week after expected ovulation (typically around day 21) can be done to confirm.
Diagnosis in adolescents differs and is often difficult as features such as acne and irregular periods can be common in this group as part of normal development. Measuring androgens can be done with levels expected to reach adult ranges by 12-15 years. Often young women are on the oral contraceptive pill and ceasing this for three months is likely to be disruptive without much benefit. If diagnosis seems likely then reassessment is recommended 8 years post menarche.
Once the diagnosis has been made it is important to assess for other conditions associated with PCOS. Screening questions for obstructive sleep apnoea should be asked regardless of weight as this is increased in all women. If daytime sleepiness and snoring are revealed then a formal questionnaire and possibly sleep studies should be undertaken. Measurement of blood glucose control and testing for diabetes can be done at diagnosis and then 3 yearly with an oral glucose tolerance ideally or an HBA1c or fasting glucose level. There is no role for testing insulin. Although there is also an increased risk of endometrial cancer in women with PCOS there is no specific screening and the actual likelihood of this is low. In those with prolonged amennorrhoea, type two diabetes and obesity the risk is increased. Endometrial biopsy should be performed and a withdrawal bleed initiated medically if the endometrium is thickened on ultrasound scan.
One of the less commonly addressed associations with PCOS is mood disorder including anxiety and depression. Psychological features are known to be present in 75-80% of women and are often not considered. It is paramount to assess what specific concerns or features of disease burden are present and consider quality of life so the woman’s own goals can be prioritized with respect to treatment aims and support needed. Assessment of mental state and referral should be undertaken. Disordered eating should likewise be considered regardless of weight.
The mainstay of management of PCOS remains centered around lifestyle. Developing and maintaining a healthy lifestyle is paramount not only for fertility and pregnancy outcomes but for risk mitigation for all associated conditions discussed above. Even in the absence of weight loss a healthy lifestyle has far reaching and long term benefits. It is worthwhile to ask permission to discuss weight and exercise as for some this can be particularly triggering or distressing and maintaining trust in this relationship is crucial.
Goal setting with “SMART” goals can assist in empowering women to reach the milestones they want and need to. In this model goals are more likely to be achieved when they are Specific Measurable, Achievable, Realistic and Timely. There is no one diet or exercise regime to follow as many will give good results, consistency is key. Maintaining weight can be achieved by 150-300 minutes of moderate or 75-150 minutes of vigorous intensity aerobic activity per week plus two sessions of muscle strengthening per week. For weight loss 250 or 150 minutes plus 2 strengthening exercises per week should be carried out. These activities may be incidental exercise as well as planned and specific work outs.
Pharmacological management is largely off label and this must be discussed with the reassurance of its use being part of a large international clinical guideline. Metformin helps to decrease insulin resistance and thus insulin levels which has the effect of a reduction in androgen synthesis to aid in improving hyperandrogenic symptoms and possibility restoring menstrual regularity and ovulation. This should be used in those who are overweight or obese and considered in those in the normal weight range. Gastrointestinal side effects are common but typically mild and self limiting, even so graduated dosing is recommended to maintain adherence starting with 500mg per day and increasing every 1-2 weeks up to a maximum dose of 2g per day in adolescents and 2.5g per day in adults. There is superior data on metformin over inositol supplementation but given likelihood of limited harm if metformin is not tolerated inositol could be considered as second line for improving metabolic factors without any proven benefit on clinical outcomes such as ovulation.
The combined oral contraceptive pill is not appropriate in those trying to conceive but does work well to manage symptoms prior to this. If menstrual irregularity is the main concern this is more effective than metformin alone. Lower doses and formulations not containing cyproterone acetate should be first line eg containing <35mcg of ethinylestrodiol however if not successful in controlling symptoms a higher dose or addition of cyproterone acetate may be beneficial.
A popular new addition are pharmacological weight loss medications such as the GLP-1 receptor agonist eg semaglutide (Ozempic). These medications do have good results for weight loss however the safety data in pregnancy is lacking so this should be used to optimize weight prior to pregnancy rather than while trying to conceive.
Pregnancy can usually be achieved with lifestyle modifications or simple ovulation induction treatment in the absence of other factors affecting fertility. Achieving ovulation is typically done with oral letrozole medication as this is simple and effective with a low risk profile. Metformin can help and it is worth starting this if a woman has to wait to see a fertility specialist who can start specialized medications. Failing this, injections of follicle stimulating hormone, as are used in IVF, can be used at lower doses to induce ovulation. The increased chance of having a multiple pregnancy such as twins is considerably higher however. If a women is resistant to oral medication or is having an operation for other purposes a procedure called ovarian drilling can be performed whereby small holes are made with cautery in the ovary resulting in spontaneous ovulation due to the reduction in androgens and insulin resistance resulting. IVF is of course an excellent back up with many having good ovarian reserve and thus high egg and embryo numbers achievable. These pregnancies must be considered as increased risk pregnancies based on the higher rates of gestational diabetes, hypertension, pre-eclampsia, pre-term delivery and caesarean section among others.
Overall women with PCOS have a very good prognosis for achieving pregnancy and should be reassured about this. Importantly those not wanting to become pregnant should be offered contraception as ovulation precedes a period and can occur without any warning.
Written by Dr Sylvia Ross
Dr Sylvia Ross is a dedicated medical professional with over a decade of experience in the field of women's health. She is a specialist in Obstetrics and Gynaecology (FRANZCOG) and currently in the final stage of completing her Certificate of Reproductive Endocrinology and Infertility (CREI), a highly competitive program producing board certified subspecialists in infertility.
Specialising in infertility treatment, Sylvia offers a range of services to support individuals and couples facing fertility issues. Her expertise includes management of polycystic ovarian syndrome, ovulation induction, in vitro fertilisation (IVF), and various surgical interventions tailored to meet the unique needs of her patients.